Telmisartan / Hydrochlorothiazide

Pronunciation: TEL-mi-SAR-tan/HYE-droe-KLOR-oh-THYE-a-zide)
Class: Antihypertensive combination

Trade Names

Micardis HCT
- Tablets, oral telmisartan 40 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral telmisartan 80 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral telmisartan 80 mg/hydrochlorothiazide 25 mg

Micardis Plus (Canada)

Pharmacology

Telmisartan

Antagonizes the effect of angiotensin II (vasoconstriction and aldosterone secretion) by blocking the angiotensin II (AT ₁ receptor) in vascular smooth muscle and the adrenal gland, producing decreased BP.

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Hydrochlorothiazide

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

For the treatment of hypertension.

Contraindications

Anuria; hypersensitivity to sulfonamide-derived drugs or any component of this product.

Dosage and Administration

Adults Current telmisartan users

PO Patients whose BP is not adequately controlled with telmisartan 80 mg monotherapy may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg once daily, and finally titrated up to 160/25 mg, if necessary.

Current hydrochlorothiazide users

PO A patient whose BP is inadequately controlled by hydrochlorothiazide 25 mg once daily may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg or telmisartan 80 mg/hydrochlorothiazide 25 mg once daily. If BP remains uncontrolled after 2 to 4 wk of therapy, the dose may be titrated up to telmisartan 160 mg/hydrochlorothiazide 25 mg, if necessary. Those patients controlled by hydrochlorothiazide 25 mg but who experience hypokalemia with this regimen may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg once daily.

Hepatic function impairment
Adults

PO Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision using the 40/12.5 mg combination.

General Advice

• Administer with or without food.
• The fixed-dose combination is not indicated for initial therapy.
• The combination may be substituted for the titrated components.
• May be given with other antihypertensive agents.

Storage/Stability

Store between 59° and 86°F. Do not remove tablets from blister packs until immediately before administration.

Drug Interactions

No drug interaction studies have been conducted between telmisartan/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the telmisartan/hydrochlorothiazide combination.

ACE inhibitors (eg, captopril, ramipril)

Concurrent use may be associated with an increased risk of renal dysfunction and hyperkalemia. Consider monotherapy. Coadministration with ramipril is not recommended.

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur.

Aliskiren

Renal excretion of potassium may be decreased, resulting in hyperkalemia, particularly in diabetic patients. Use alternatives to aliskiren in diabetic patients. If coadministration is undertaken, closely monitor serum potassium concentrations.

Amantadine

The incidence of toxic effects of amantadine may be increased. Consider reducing the dose of amantadine.

Antihypertensives (eg, propranolol)

Additive or potentiation of hypotensive effects may occur.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol resins

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide, reducing GI absorption up to 85% and 43%, respectively. Separate the administration times by at least 4 h. Adjust diuretic dose as needed.

Cyclooxygenase 2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen, indomethacin, ketorolac [nasal])

The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide and the antihypertensive effects of telmisartan may be reduced. In addition, concomitant use may further deteriorate renal function, especially in volume-depleted patients, patients with renal impairment, or in elderly patients. The risk of hyperkalemia may also be increased. Monitor BP, renal function, and serum potassium. If an interaction is suspected, it may be necessary to discontinue the NSAID.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Closely monitor plasma concentrations of potassium and magnesium and monitor patients for signs of digoxin toxicity.

Dofetilide

Plasma concentrations of dofetilide may be increased; prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Insulin

Insulin requirements may increase, decrease, or remain unchanged. Monitor blood glucose and adjust the insulin dose as needed.

Loop diuretics (eg, furosemide)

The effects of loop diuretics may be decreased. In contrast, loop diuretics and hydrochlorothiazide have synergistic effects that may result in profound diuresis and electrolyte abnormalities. Monitor fluid status and electrolytes.

Lithium

Lithium Cl may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Avoid coadministration. If coadministration cannot be avoided, closely monitor serum lithium levels and adjust the dose of lithium as needed.

Nondepolarizing muscle relaxants (eg, tubocurarine)

A possible increase in responsiveness to the muscle relaxant due to diuretic-induced hypokalemia may occur. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

Potassium preparations (eg, potassium-sparing diuretics [eg, amiloride, spironolactone], potassium supplements, salt substitutes containing potassium)

Serum potassium concentrations may be increased, decreased, or unchanged. Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Closely monitor serum potassium concentrations. Adjust treatment as needed.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.

Sulfonylureas (eg, glyburide)

Hydrochlorothiazide may increase fasting blood glucose and decrease the hypoglycemic action of sulfonylureas. Closely monitor blood glucose and adjust therapy as needed.

Tretinoin

The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.

Trimethoprim

Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur, especially in elderly patients. Closely monitor serum potassium. Adjust therapy as needed.

Laboratory Test Interactions

Hydrochlorothiazide may decrease serum protein-bound iodine levels without signs of thyroid disturbance. Interrupt therapy for a few days before carrying out tests of parathyroid function.

Adverse Reactions

Cardiovascular

Postural hypotension, tachycardia (less than 2%); atrial fibrillation, bradycardia, CHF, hypertension, hypertension aggravated, hypotension, MI, syncope (postmarketing).

CNS

Dizziness (5%); fatigue (3%); asthenia, headache, weakness (postmarketing).

Dermatologic

Rash (less than 2%); drug eruption (toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), erythema, sweating increased, urticaria (postmarketing).

GI

Diarrhea (3%); nausea (2%); abdominal pain, dyspepsia, vomiting (less than 2%).

Genitourinary

Erectile dysfunction, renal impairment including acute renal failure, UTI (postmarketing).

Hepatic

Elevated liver enzymes and/or serum bilirubin; abnormal hepatic function/liver disorder (postmarketing).

Hematologic

Anemia, eosinophilia, thrombocytopenia (postmarketing).

Hypersensitivity

Anaphylactic reaction, angioedema with fatal outcome, angioneurotic edema, hypersensitivity (postmarketing).

Lab Tests

Increased BUN (3%); decreased Hgb and Hct, increased serum creatinine (1%); increased CPK, increased uric acid (postmarketing).

Metabolic

Hypokalemia (less than 2%); edema, hypercalcemia, hyperglycemia, hyperuricemia, hypomagnesemia, hyponatremia, increased triglyceride and cholesterol levels; hyperkalemia, hypoglycemia in diabetic patients (postmarketing).

Musculoskeletal

Back pain (less than 2%); lower limb edema, muscle cramps including leg cramps, myalgia, tendon pain including tendonitis and tenosynovitis (postmarketing).

Respiratory

Upper respiratory tract infection (8%); bronchitis (less than 2%); cough (postmarketing).

EENT

Sinusitis (4%); pharyngitis (less than 2%).

Miscellaneous

Influenza-like symptoms (2%); chest pain, facial edema, pain (postmarketing).

Precautions

Warnings When pregnancy is detected, discontinue therapy as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Monitor Correct volume and/or salt depletion before initiating therapy. Observe all patients for clinical signs of fluid or electrolyte imbalance. Evaluate renal function and measure serum electrolytes before starting therapy and periodically thereafter. Monitor BP and pulse on a regular basis. Monitor blood glucose in diabetic patients when the drug is started or dose is changed.

Pregnancy

Category D . Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Lactation

It is not known if telmisartan is excreted into breast milk. Thiazides appear in breast milk. A decision should be made whether to discontinue breast-feeding or the drug, taking into account the importance of the drug to the woman.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Hypersensitivity

May occur in patients with or without history of allergy or bronchial asthma; cross-sensitivity with sulfonamides also may occur.

Renal Function

Not recommended in patients with severe renal impairment (CrCl less than 30 mL/min). Thiazides may precipitate azotemia in these patients, and the effects of repeated dosing may be cumulative. In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported.

Hepatic Function

Not recommended in severe hepatic impairment. Use with caution in patients with mild to moderate hepatic function or progressive liver disease because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Diabetics

Hyperglycemia may occur; latent diabetes mellitus may become manifest.

Electrolyte imbalance

Hyperkalemia, hypokalemia, hyponatremia, hypochloremic alkalosis, hypercalcemia, and hypomagnesemia may occur.

Hyperuricemia

May occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Hypotension

Symptomatic hypotension may occur after initiation of therapy in patients who are intravascularly volume or sodium depleted (eg, those treated with diuretics). Use with caution in these patients. Correct these conditions prior to administration or start treatment under close medical supervision.

Lipid disorders

Increases in cholesterol and triglyceride levels may occur.

Ocular effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms typically occur within hours to weeks of initiation of therapy.

Postsympathectomy

The antihypertensive effects may be enhanced in these patients.

Renal effects

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors has been associated with oliguria and/or progressive azotemia, and, rarely, with acute renal failure and/or death. In addition, increased BUN and serum creatinine may occur.

Systemic lupus erythematosus

Exacerbation or activation may occur.

Overdosage

Symptoms

Bradycardia, dehydration, dizziness, electrolyte depletion (eg, hypochloremia, hypokalemia, hyponatremia), hypotension, tachycardia.

Patient Information

• Inform female patients of childbearing age about the consequences of exposure to telmisartan/hydrochlorothiazide during pregnancy. Discuss treatment options with women planning to become pregnant. Advise patients to report pregnancies to their health care provider as soon as possible.
• Caution patients that light-headedness can occur, especially during the first few days of therapy, and that it should be reported to the prescribing health care provider. Inform patients that if syncope occurs, telmisartan/hydrochlorothiazide should be discontinued until the health care provider has been consulted.
• Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, with the same consequences of light-headedness and possible syncope.
• Advise patients not to use potassium supplements or salt substitutes containing potassium without consulting their health care provider.

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